In pelvic reconstruction surgery, the hemipelvic prosthesis can cause significant changes in stress distribution due to its high stiffness, and its solid structure is not suitable for osseointegration. The purpose of this study was to identify a novel bone mineral density screw channel and design the structure of the prosthesis so as to improve the distribution of stress, promote bone growth, and enhance the biomechanical properties of the prosthesis. The mechanical characteristics of bone mineral density screw and traditional screw were compared by finite element analysis method, and redesigned by topology optimization. The direction of the newly proposed screw channel was the posterolateral entrance of the auricular surface, ending at the contralateral sacral cape. Compared to the original group, the maximum stress of the optimized prosthesis was decreased by 24.39%, the maximum stress of the sacrum in the optimized group was decreased by 27.23%, and the average strain energy density of the sacrum in the optimized group was increased by 8.43%. On the surface of screw and connecting plate, the area with micromotion more than 28 μm is reduced by 12.17%. On the screw surface, the area with micromotion more than 28 μm is reduced by 22.9%. The newly determined screw channel and optimized prosthesis design can effectively improve the biomechanical properties of a prosthesis and the microenvironment of osseointegration. This method can provide a reference for the fixation of prostheses in clinical pelvic reconstruction.